The experiments proposed in this application focus on the mechanistic basis for damage from ionizing radiation. We specifically ask "How does radiation damage the cell?" "What role do radiolytic products play in this damage?" "How does oxygen function as a radiation sensitizer?" We plan experiments with bacteria (multiple strains of E. coli), the mammalian (human) erythrocyte, and a chemical assay for measuring the radiolytic yeilds of hydrogen peroxide. Because an organism's overall response to ionizing radiation involves many factors, complementary experiments with different types of cells are required. Bacterial spores are metabolically inactive and, therefore, enzymatically directed repair is not possible. Our past work with spores identifies the kinds of radiation-induced damage which can occur. Complementary experiments with different mutant strains of bacteria will allow us to judge whether or not we can associate a specific type of repair with a particular kind of radiation-induced damage. Work with cell membranes will show whether or not we can identify a specific cellular target for damage from ionizing radiation. Although these experiments involve chemical systems and procaryotic cells, the required parallel work with in vitro mammalian cells is underway (1 RO 1 CA-28932). The information we gain with these biological and chemical systems should have immediate clinical relevance. Our long-range goals involve applying this information to select and test sensitizers in combination with oxygen. When sensitizers are found which function differently from oxygen, the overall effect from combinations of oxygen and such a sensitizer should be at a maximun. This means we would achieve a higher clinical effectiveness when tumors containing cells at low oxygen concentrations are treated. The basis for such an application is a thorough knowledge of how radiation damages cells and how oxygen functions as a radiation sensitizer.